The present invention is directed to sensors and, more particularly, sensors of the type that are fabricated using solid state fabrication techniques such as, for example, complimentary metal oxide semiconductor (CMOS) techniques.
Over the last 30 years, significant improvements have been made in techniques and equipment used to fabricate miniature devices and, consequently, the use of micromachined equipment is widespread in any modern society. Improvements in silicon manufacturing and high-precision machinery opened the area now known as Micro-ElectroMechanical Systems (MEMS) for research and development of applications. Subsequent development of microscale valves, pumps, channels and heat exchangers allowed for manipulation of extremely small fluid volumes. Coupled with mass fabrication techniques refined in the integrated circuit (IC) and MEMS communities, microfluidic and microchemical systems are now starting to find their way into industrial use.
A major application area is the development of sensors, most of which are custom made. Environmental sensors which continuously monitor their surroundings to provide background statistics and warnings against unhealthy conditions are known to be used in cities, sea and air. In such applications, microscale solutions are sought for reasons of minimum cost and impact as well as long lifetime due to limited use of consumables. More advanced configurations include coordinated and flexible sensor systems with multiple devices operating on a single fluid sample to carry out fully automated chemical analysis with the aid of on-board processing logic. Examples range from DNA separation and analysis arrays to personal chemical warfare sensors. A recent report from the World Technology Evaluation center provides an excellent overview of the different technological approaches used. Common to all sensor projects is the desire to create transducers capable of identifying small amounts of interesting or harmful materials present in their environment. Auxiliary goals include detection speed, robustness, reliability and long life. Widespread use, in particular for routine medical purposes in private homes or developing countries, also requires an inexpensive device that may be operated by unskilled individuals.
The principles of acoustic wave, sometimes referred to as gravimetric sensors, are well known and applications have appeared in the literature for more than a decade. Molecular interactions can be detected electronically through the polarizability of biological macromolecules, optically through the use of fluorescencing tags, radiometrically through the use of radioactive labeled tags, or acoustically. Recently, MEMS based sensors have been incorporated in the biotechnical and biomedical fields. Application of acoustic biosensors range from cell detection, glucose biosensing, antibody-antigen recognition, and protein adsorption.
There are numerous examples of gravimetric biosensors. The basis of detection is the decrease in the resonant frequency of a resonator that occurs as analyte species attach to the resonating element. Analyte specificity is conferred for biological analytes by functionalizing (treating) the exposed surface of the resonator with ligands that recognize and bind to the target analyte species. Examples of suitable binding entities for target biological analytes include antibodies, receptors, lectins, aptamers and oligonucleotides.
Piezoelectric quartz crystal microbalances (QCMs) have been used since the late 1950s to detect gas and liquid phase analytes. Application of QCM technology to biological analytes is more recent. QCMs have been used to track the non-specific adsorption of proteins to unmodified and modified quartz crystal surface electrodes. Immobilization of antibodies to the crystal surface confers analyte specificity.
A wide variety of cantilever, membrane and piezoelectric resonator-based sensors have been fabricated using MEMS technology. Cantilever systems have been used to detect metal deposition and chemical species adsorbing to polymeric coatings (Oden, 1998; Lange et al.1998). Basic modeling approaches for cantilever beam resonances have also been described (Glumac et al., 1995). Reported membrane-based gravimetric chemical sensors typically rely on analyte adsorption to polymer films and polymer coated plates (Walton et al., 1993; Wenzel and White, 1990); recently (Wang et al., 1998) described an antibody-functionalized flexural plate-wave sensor for specific detection of cancer antigens. Finally several different piezoelectric films, operating in a similar manner to the macroscopic QCM devices, have also been proposed as gravimetric chemical sensors (Ferrari et al., 2000; Hsieh et al., 1999)
Sensors for detecting the presence of molecules of interest have application in numerous fields, including medical diagnosis, biomedical research, and detection of agents used in biological and chemical warfare. The need exists for an inexpensive, compact sensor with high sensitivity for these and other applications.